Immunochemical, biosynthetic, and structural studies on homogeneous prototypes of normal immunoglobulins, i.e., Bence Jones proteins and myeloma proteins, are proposed to elucidate the genetic mechanisms controlling immunoglobulin synthesis. A structural basis for antibody specificity is apparent from the primary structure of the light polypeptide chain, i.e., an amino terminal half with a variant amino acid sequence (VL) and a carboxyl terminal half with a constant amino acid sequence (CL). This unique structure of the light polypeptide chain has evoked fundamental questions concerning the genetic control of immunoglobulin synthesis and the contributory role of each half in the properties expressed by the intact molecule. While the extent of variability or constancy in the primary structure of the light polypeptide chain of immunoglobulins has been determined chiefly by structural analyses, it is evident that differences detected by structural analyses can be detected by immunochemical analyses. The concordance between structural and immunochemical studies of immunoglobulins asserts the importance of utilizing immunochemical techniques which provide rapid and sensitive means for detection and localization of differences on the immunoglobulin polypeptide chains. Knowledge of the properties of VL and CL is of prime importance in providing answers to these basic questions. Such information requires comparative studies on isolated VL, CL, and intact chains. The ability to cleave specifically Bence Jones proteins and light chains into VL and CL permits the preparation and isolation of each half in sufficient quantities needed for studies on the genetic control of immunoglobulin synthesis and the relationship between antibody structure and antibody specificity.